PROJECT SUMMARY/ABSTRACT The 2018 Gordon Research Conference (GRC) on Mutagenesis will focus on the causes and consequences of mutagenesis. The meeting will address topics ranging from the fundamental molecular mechanisms of mutagenesis, through the roles of mutagenesis in biology, aging and disease, to the exploitation of mutagenesis for therapy. Intrinsic and extrinsic stresses constantly challenge the genome. These genome stresses can arise from environmentally derived sources of DNA damage, as well as endogenous metabolic processes, secondary DNA structures or collisions between replication and transcription machineries. The response to these challenges determines whether mutations are created or avoided, and the type of mutation created. Increased mutation rates are associated with premature aging and cancer, and contribute to numerous other human disorders. However, mutation accumulation is also beneficial for biological processes including evolution, antibody diversification and antiviral immunity. Key themes to be explored in this GRC are the molecular mechanisms of mutagenesis, its role in human disease and therapeutic strategies that target mutagenesis. A broad range of experimental approaches will be discussed, ranging from genetics and biochemistry to bioinformatics, employing bacteria, yeast and mammals systems. This GRC will bring together 28 confirmed speakers from all career stages representing academia, industry and research institutes. Approximately 20 additional speakers will be selected from the submitted abstracts to present short talks, and at least ten posters presenters will highlight their work in poster previews. These short talks and poster previews will ensure coverage of the latest developments and help promote the inclusion of younger investigators. Students and postdocs will also benefit from the GRS, a two-day workshop organized by students and postdocs that precedes the GRC. This meeting will include eight talks selected from abstracts, a keynote lecture and a career development panel. The GRC program will be organized into 9 morning and evening sessions with sessions entitled: (1) The mechanistic origins of mutagenesis; (2) RNA-dependent mutagenesis; (3) Mutagenesis due to environmental and endogenous sources of DNA damage; (4) Damage avoidance: Lesion bypass and template switching; (5) Replication stress and the consequences of failure to complete replication; (6) Genome instability and mutagenesis in disease; (7) Mutagenesis in low complexity and repetitive sequences; (8) Understanding the origins of mutagenesis in cancer, and (9) Emerging themes in mutagenesis: from concept to clinic. Daily posters sessions will promote interactions between early career and more established researchers. There is also is ample free time for group discussions and networking, as well as for a `powerhour' on issues facing women in science and a `Meet the Editor' session. This GRC and GRS will thus promote novel collaborations, enhance and promote the careers of young scientists and exploring the latest themes, techniques and applications in the field of mutagenesis.